Amoxicillin, D-(-)-alpha-amino-parahydroxybenzyl penicillin, is a semi-synthetic penicillin produced in accordance with the processes disclosed in U.S. Pat. No. 3,674,776. Certain of its salts are also known, i.e., hydrochloric, phosphoric, sulfuric, thiocyanic and beta-naphthalene sulfonic acid salts, and sodium and potassium salts.
The compound is readily formulated into stable oral dosage forms and is useful to treat bacterial infections. Amoxicillin is practically insoluble in water and aqueous solutions and therefore cannot be incorporated satisfactorily into parenteral formulations. In addition, the known salts of amoxicillin are unsuitable for use in parenteral formulations because, inter alia, they are unstable in aqueous media or cause irritation at the site of injection.
In order to form satisfactory injectable solutions of closely related semisynthetic penicillins, e.g., ampicillin, the usual method is to dissolve the sodium salt of the compound in the sterile water for injection and administer within an hour. For administration by intravenous drip, the sodium salt is isotonic sodium chloride, 5% dextrose in 0.4% aqueous sodium chloride solution, 10% invert sugar in water or a sodium lactate solution and administered as a very dilute, e.g., 0.2%, solution of ampicillin.
These known methods of producing injectable solutions are not suitable for amoxicillin since the sodium salt of amoxicillin is prepared at a pH of about 9 and amoxicillin is very unstable at such high pH's. In fact, amoxicillin is most stable at pH 7 but is relatively insoluble at that pH.
There is thus a need for a suitable form of amoxicillin which is amenable to inclusion in parenteral formulations and which performs satisfactorily when injected into the patient and retains the antibacterial activity of amoxicillin.